Dna Chips and the Pharmaceutical Industry

DNA CHIPS AND THE PHARMACEUTICAL INDUSTRY

INTRODUCTION

When future historians look back on the greatest scientific advancements of the 20th century, they will without a doubt focus on only three events: the Apollo Moon landing, the invention of the microprocessor, and possibly the greatest scientific endeavor yet, genomics, the science of identifying genes and how they work in humans. It is possibly not a total coincidence then that two of this centuries greatest advancements have grown out of the same cradle of technology, Silicon Valley. The first advancement was the invention of the microprocessor, and the second was the invention of the DNA chip, also called the DNA array or biochip.

These DNA chips are the newest tools being used in the study of genomics. DNA chips are changing the way researchers analyze the genetic make-up of cells, and will soon render traditional pharmaceutical research obsolete. This allows for whole new generations of drugs that will be made to combat diseases by effecting changes in a their specific genetic design.

PROBLEM STATEMENT

Currently the pharmaceutical industry is a very high risk industry in which fewer than one in ten promising drug products ever makes it through the testing phase and onto the shelves at the local pharmacy. The effect is that the production of a new drug is almost like a guessing game that may or may not produce any profit. A Company may have a long list of chemicals that could make possible drugs to treat a specific affliction, but by the time they narrow the list down, and do the necessary research and testing, they may have already spent possibly millions of dollars. In the end they may not even be left with a viable drug to market.

BACKGROUND

This section is designed to educate the reader on some of the background information needed to understand the nature of DNA chips, as well as to appreciate the benefits the chips could bring to pharmaceutical research. This section consists of the following sections: The Definition of DNA Chips, and The Pharmaceutical Industry Today.

The Definition of DNA Chips

DNA chips bear an amazing resemblance to microchips. DNA chips are basically pieces of silicon that are layered with a dense checkerboard-like grid of sites called features [2]. There are typically anywhere from 100,000 to 500,000 of these features on any given 2X2cm DNA chip. Attached at each feature are millions of copies of a single segment of DNA, which acts as a DNA probe. Each segment of DNA can range from a few nucleotides, to millions. Nucleotides are the chemical building blocks of DNA. There are only four nucleotides that make up every single strand of DNA in every living creature: adenine, guanine, cytosine, and thymine.

Any genetic material being tested is first labeled with a fluorescent marker. When the marked DNA is applied to the DNA chip, any strands of marked DNA whose nucleotide sequence is complimentary to the sequence of a given DNA probe, will hybridize to the DNA probe and hence "stick" to the chip. Any other marked DNA that does not compliment one of the particular sequences of a probe on the chip, will not stick, and can be washed away. Even DNA segments that partially complement and bond with the DNA of the probe, will be washed away with a 97 percent success rate.

Carefully designed arrays of DNA probes can give the DNA chip the ability to represent an entire genes nucleotide sequence. Such chips can reveal visually, via hundred thousand-dollar read-out displays, whether the DNA sample being tested differs by even a single nucleotide from the standard version. When there may be millions of nucleotides in a given sample, being able to identify one that doesn't match is a tremendous feat.

The technology that spawned the DNA chip became a reality in the early 1990's, after the commencement of the Human Genome Project (HGP). The HGP was started in 1990 and is one of the most ambitious endeavors ever undertaken by mankind. It is a government funded project whose two major goals are to identify the 80,000 to 100,000 genes in human DNA, and to determine the nucleotide sequences of the 3 billion or so chemical bases that make-up human DNA. The genes in human DNA largely determine every physical characteristic, and possibly many mental characteristics that define what a human being is. It is our genes that make us different from every other living creature. The chemical codes that make up these genes are in effect a "book of life."

The HGP was expected to be completed in the year 2005, but several technological advancements, such as DNA chips, have pushed the expected completion date at least 4 years forward to 2001. The major difference between DNA chips and previous DNA sequencing technologies is not in what the chips do, but in the manner of how it is done. Previous methods of gene sequencing focused on analyzing only one gene at a time, and to analyze one could take several weeks. By utilizing DNA chip technology, literally thousands of genes can be analyzed and identified simultaneously and all this can be accomplished within days or even hours. Previous technologies would cost thousands of dollars to analyze one gene, but DNA chips can accomplish the same task for a hundred dollars or less per gene.

The idea behind DNA chips is that the sequence of a standard DNA sample must be known before a chip can be of use. Once this sequence is identified a chip is tailor-made to search for that particular sequence or sequences, and match it to the DNA of a sample. It is feasible that within the next decade, after the human genetic design has been analyzed and established, a DNA chip will be made that will have the ability to analyze a few cell samples of an individual, and within hours or possibly even minutes, determine if and exactly how that persons gene make-up differs from the standard human gene make-up. There could possibly be hundreds of genetic differences. Any one of these differences could be the cause of a specific type of ailment or cause a genetic predisposition to a certain type of ailment. So in effect, this technology gives science the potential ability to analyze the specific genetic make-up of every living creature on earth, by determining how that creatures genetic make-up differs from a standard known genetic make-up. Once all of this information is known, the